Studies were carried out to examine the role of lysosomal lipases and phospholipases in human disease. Acid lipase was measured in leukocytes of 96 subjects undergoing coronary arteriography. Analysis indicated no positive or negative correlation of lysosomal lipase activity with the presence or absence of atherosclerosis. The ability of acid lipase to hydrolyze cholesterol lignocerate was investigated to evaluate a report of a specific acid lipase isozyme deficiency in adrenoleukodystrophy. Cholesterol lignocerate was not hydrolyzed by acid lipase deficient cells but was hydrolyzed by adrenoleukodystrophy fibroblasts, indicating no acid lipase deficiency in adrenoleukodystrophy. Assay conditions were established for lysosomal phospholipases Al, A2, and C in human fibroblasts. These studies indicated the presence of normal levels of these three enzyme activities in acid lipase deficient cells. In sphingomyelinase deficient cells, however, there was also deficiency of phospholipase C when assayed with phosphatidyl choline substrate. These studies suggest a relationship between phospholipase C activity in cultured fibroblasts and sphingomyelinase. No enzmye deficiencies were detected in a variety of disease states, including neuronal ceroid lipofuscinosis and sea blue histiocyte disease.